Citations

Background Minimally invasive (MIS) treatment of hallux valgus (HV) deformity is increasing in popularity. A 2-mm diameter burr is used to create a distal first metatarsal osteotomy prior to capital fragment translation and fixation. The metatarsal will shorten by the burr’s diameter (2 mm). Plantar or dorsal capital fragment displacement may also cause load transference and possibly transfer metatarsalgia. The purpose of this study is to examine the effect of MIS HV on forefoot loading mechanics with respect to metatarsal shortening and sagittal plane displacement. Methods Four lower-limb cadaveric specimens were studied. A pedobarography pressure-sensing mat was used to record forefoot plantar pressure in a controlled weight-bearing stance position. Control and postosteotomy measurements were obtained with the capital fragment fixated in 3 possible positions: 0 mm, 5 mm dorsal, and 5 mm plantar displacement. Pedobarography data yielded pressure data within measurable graphical depictions. Raw mean contact pressure measurements were taken under the first and fourth metatarsal heads to establish medial and lateral forefoot loading pressure ratios. An a priori power analysis was performed based on previous peer-reviewed pedobarographic data, and our study was adequately powered. Results Around 40 measurements were recorded, and ratios of medial-to-lateral forefoot loading were constructed. Medial forefoot pressure control versus 0 mm displacement, and control versus dorsal displacement were not found to be statistically significant ( p = 0.525, p = 0.55, respectively). Medial pressure significantly increased when comparing control versus plantar displacement ( P = .006). Lateral pressure significantly increased with dorsal displacement of the osteotomy ( P = .013). Conclusion Our study found that MIS HV correction did not cause an increase in lateral forefoot pressure loading when sagittal plane displacements were controlled. Plantar displacement increased medial loading, and dorsal displacement increased lateral loading. It may be valuable for surgeons to consider metatarsal head position postosteotomy, as a decrease in medial loading and subsequent increase in lateral loading may lead to lateral forefoot pain and transfer metatarsalgia. Levels of Evidence: IV.

Importance Half of all carriers of inherited cancer-predisposing variants in BRCA1 and BRCA2 are male, but the implications for their health are underrecognized compared to female individuals. Germline variants in BRCA1 and BRCA2 (also known as pathogenic or likely pathogenic variants, referred to here as BRCA1/2 PVs) are well known to significantly increase the risk of breast and ovarian cancers in female carriers, and knowledge of BRCA1/2 PVs informs established cancer screening and options for risk reduction. While risks to male carriers of BRCA1/2 PVs are less characterized, there is convincing evidence of increased risk for prostate cancer, pancreatic cancer, and breast cancer in males. There has also been a rapid expansion of US Food and Drug Administration–approved targeted cancer therapies, including poly ADP ribose polymerase (PARP) inhibitors, for breast, pancreatic, and prostate cancers associated with BRCA1/2 PVs. Observations This narrative review summarized the data that inform cancer risks, targeted cancer therapy options, and guidelines for early cancer detection. It also highlighted areas of emerging research and clinical trial opportunities for male BRCA1/2 PV carriers. These developments, along with the continued relevance to family cancer risk and reproductive options, have informed changes to guideline recommendations for genetic testing and strengthened the case for increased genetic testing for males. Conclusions and Relevance Despite increasing clinical actionability for male carriers of BRCA1/2 PVs, far fewer males than female individuals undergo cancer genetic testing. Oncologists, internists, and primary care clinicians should be vigilant about offering appropriate genetic testing to males. Identifying more male carriers of BRCA1/2 PVs will maximize opportunities for cancer early detection, targeted risk management, and cancer treatment for males, along with facilitating opportunities for risk reduction and prevention in their family members, thereby decreasing the burden of hereditary cancer.

OBJECTIVE Cerebral revascularization surgery (CRS) has been used to prevent stroke in children with sickle cell disease (SCD) and cerebral vasculopathy (e.g., moyamoya syndrome). While results suggest that it may be an effective treatment, surgical indications have not been well defined. This study sought to determine indications for offering revascularization surgery in centers with established sickle cell programs in the US. METHODS Three sequential surveys utilizing the Delphi methodology were administered to neurosurgeons participating in the Stroke in Sickle Cell Revascularization Surgery study. Respondents were presented with clinical scenarios of patients with SCD and varying degrees of ischemic presentation and vasculopathy, and the group’s agreement to offer surgical revascularization was measured. Consensus was defined as ≥ 75% similar responses. RESULTS The response rate to all 3 surveys was 100%. Seventeen neurosurgeons from 16 different centers participated. The presence of moyamoya collaterals (MMCs) and arterial stenosis matching an ischemic distribution yielded the strongest recommendations to offer surgery. There was consensus to offer revascularization in the presence of MMCs and at least 50% arterial stenosis matching an ischemic distribution. In contrast, there was no consensus to offer revascularization with 50%–70% stenosis not matching an ischemic presentation in the absence of MMCs. The presence of the ivy sign in the distribution of the stenotic artery also contributed to the consensus to offer surgery in certain scenarios. CONCLUSIONS There were several clinical scenarios that attained consensus to offer surgery; the strongest was moderate to severe arterial stenosis that matched the distribution of ischemic presentation in the presence of MMCs. Radiological findings of decreased cerebral flow or perfusion also facilitated attaining consensus to offer surgery. The findings of this study reflect expert opinion about questions that deserve prospective clinical research. Determination of indications for CRS can guide clinical practice and aid the design of prospective studies.

Abstract This study explored the role of the ubiquitin-proteasome system (UPS) in dominantly inherited Alzheimer’s disease (DIAD) by examining changes in cerebrospinal fluid (CSF) levels of UPS proteins along with disease progression, AD imaging biomarkers (PiB PET, tau PET), neurodegeneration imaging measures (MRI, FDG PET), and Clinical Dementia Rating® (CDR®). Using the SOMAscan assay, we detected subtle increases in specific ubiquitin enzymes associated with proteostasis in mutation carriers (MCs) up to two decades before the estimated symptom onset. This was followed by more pronounced elevations of UPS-activating enzymes, including E2 and E3 proteins, and ubiquitin-related modifiers. Our findings also demonstrated consistent correlations between UPS proteins and CSF biomarkers such as Aβ42/40 ratio, total tau, various phosphorylated tau species to total tau ratios (ptau181/T181, ptauT205/T205, ptauS202/S202, ptauT217/T217), and MTBR-tau243, alongside Neurofilament light chain (NfL) and the CDR®. Notably, a positive association was observed with imaging markers (PiB PET, tau PET) and a negative correlation with markers of neurodegeneration (FDG PET, MRI), highlighting a significant link between UPS dysregulation and neurodegenerative processes. The correlations suggest that the increase in multiple UPS proteins with rising tau levels and tau-tangle associated markers, indicating a potential role for the UPS in relation to misfolded tau/neurofibrillary tangles (NFTs) and symptom onset. These findings indicate that elevated CSF UPS proteins in DIAD MCs could serve as early indicators of disease progression and suggest a link between UPS dysregulation and amyloid plaque, tau tangles formation, implicating the UPS as a potential therapeutic target in AD pathogenesis.

Importance The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. Objective To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. Design, Setting, and Participants Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. Interventions For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. Main Outcomes and Measures The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. Results Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P < .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P < .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No new safety risks were detected in the treatment groups. Conclusion and Relevance Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. Trial Registration ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135

AbstractPurposeTo assess the practicality of employing a commercial knowledge‐based planning tool (RapidPlan) to generate adapted intact prostate and prostate bed volumetric modulated arc therapy (VMAT) plans on iterative cone‐beam computed tomography (iCBCT) datasets.Methods and materialsIntact prostate and prostate bed RapidPlan models were trained utilizing planning data from 50 and 44 clinical cases, respectively. To ensure that refined models were capable of producing adequate clinical plans with a single optimization, models were tested with 50 clinical planning CT datasets by comparing dose‐volume histogram (DVH) and plan quality metric (PQM) values between clinical and RapidPlan‐generated plans. The RapidPlan tool was then used to retrospectively generate adapted VMAT plans on daily iCBCT images for 20 intact prostate and 15 prostate bed cases. As before, DVH and PQM metrics were utilized to dosimetrically compare scheduled (iCBCT Verify) and adapted (iCBCT RapidPlan) plans. Timing data was collected to further evaluate the feasibility of integrating this approach within an online adaptive radiotherapy workflow.ResultsModel testing results confirmed the models were capable of producing VMAT plans within a single optimization that were overall improved upon or dosimetrically comparable to original clinical plans. Direct application of RapidPlan on iCBCT datasets produced satisfactory intact prostate and prostate bed plans with generally improved target volume coverage/conformality and rectal sparing relative to iCBCT Verify plans as indicated by DVH values, though bladder metrics were marginally increased on average. Average PQM values for iCBCT RapidPlans were significantly improved compared to iCBCT Verify plans. The average time required [in mm:ss] to generate adapted plans was 06:09 ± 02:06 (intact) and 07:12 ± 01:04 (bed).ConclusionThis study demonstrated the feasibility of leveraging RapidPlan to expeditiously generate adapted VMAT intact prostate and prostate bed plans on iCBCT datasets. In general, adapted plans were dosimetrically improved relative to scheduled plans, emphasizing the practicality of the proposed approach.

Abstract Background Pulsed‐field ablation (PFA) has emerged as an innovative alternative to radiofrequency (RF) and cryoablation because it selectively targets myocardial tissue. Thus, we aim to estimate the efficacy and safety of PFA versus thermal ablation for atrial fibrillation (AF) ablation. Methods A systematic review and meta‐analysis were retrieved from PubMed, WOS, SCOPUS, EMBASE, and CENTRAL through September 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). PROSPERO ID: CRD42023480321 Results We included 17 studies with a total of 2255 patients. PFA was significantly associated with a decreased incidence of AF recurrence (RR: 0.66 with 95% CI [0.51, 0.87], p = .003). However, there was no significant difference between PFA and thermal ablation in arrhythmia recurrence (RR: 0.92 with 95% CI [0.74, 1.46], p = .42). PFA was significantly associated with decreased total procedure time (MD: −15.15 with 95% CI [−20.23, −10.07], p < .00001), decreased heart rate change (MD: −7.39 with 95% CI [−12.16, −2.62], p = .002), decreased phrenic nerve palsy (RR: 0.38 with 95% CI [0.15, 0.98], p = .05), and reduced esophageal lesions (RR: 0.09 with 95% CI [0.01, 0.69], p = .02). On the contrary, PFA was significantly associated with increased pericardial tamponade (RR: 6.14 with 95% CI [1.43, 26.33], p = .01). Conclusion PFA was significantly associated with decreased AF recurrence, total procedure time, heart rate change, phrenic nerve palsy, esophageal lesion, and increased incidence of pericardial tamponade compared with thermal ablation.

Abstract Background Artificial intelligence (AI) has emerged as a tool to potentially increase the efficiency and efficacy of cardiovascular care and improve clinical outcomes. This study aims to provide an overview of applications of AI in cardiac surgery. Methods A systematic literature search on AI applications in cardiac surgery from inception to February 2024 was conducted. Articles were then filtered based on the inclusion and exclusion criteria and the risk of bias was assessed. Key findings were then summarized. Results A total of 81 studies were found that reported on AI applications in cardiac surgery. There is a rapid rise in studies since 2020. The most popular machine learning technique was random forest ( n = 48), followed by support vector machine ( n = 33), logistic regression ( n = 32), and eXtreme Gradient Boosting ( n = 31). Most of the studies were on adult patients, conducted in China, and involved procedures such as valvular surgery (24.7%), heart transplant (9.4%), coronary revascularization (11.8%), congenital heart disease surgery (3.5%), and aortic dissection repair (2.4%). Regarding evaluation outcomes, 35 studies examined the performance, 26 studies examined clinician outcomes, and 20 studies examined patient outcomes. Conclusion AI was mainly used to predict complications following cardiac surgeries and improve clinicians' decision‐making by providing better preoperative risk assessment, stratification, and prognostication. While the application of AI in cardiac surgery has greatly progressed in the last decade, further studies need to be conducted to verify accuracy and ensure safety before use in clinical practice.